What are age-related diseases?

If we want to make progress against aging and age-related disease, we should define what these are.

There is considerable debate around defining aging. A 2018 review paper notes, "Nowadays one of the most crucial questions of the biological aging research is to determine what is aging per se" [1].

One way to define aging is lifespan and death rates by age. One main reason aging can be terrible is that your risk of death grows exponentially.

This figure, based on mortality data of Japanese women, shows that your likelihood of death increases exponentially with age [2]. Thus, one way to define aging is lifespan and death rates by age. Progress would mean increased lifespan and decreased death rates by age.

But what are the diseases associated with death? We can look at CDC-reported causes of death.

This table shows the top 15 CDC-reported causes of death in 2019 [3]. Most of these are related to age (heart disease, cancer, Alzheimer's, diabetes, etc), but also have major lifestyle components (e.g. diet, exercise, smoking). Progress would be mitigating these diseases.

What are the causes of these diseases? There are "hallmarks of aging" that attempt to provide molecular/cellular of the aging diseases we experience [4]. These include "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication." Progress would be keeping the hallmarks of aging in more youthful states.

Where should researchers focus? Increasing overall lifespan? Addressing age-related causes of death? Working on hallmarks of aging? Any single disease or aging hallmarks are enough to make a long scientific career. For example, Judy Campisi has made critical progress in understanding cellular senescence (one of the nine listed hallmarks of aging) over a multi-decade career.

My approach is first, to maintain a north star of the impact I want to have, which is increasing average healthy lifespan for humanity. Next, I am trying to be open and interdisciplinary. I try to read widely across hallmarks of aging, biochemistry, aging disease, etc. I will certainly end up focusing somewhere (I am surrounded by world-class neuroscientists at UCSF...). But I don't need to do that yet.



References

[1] Vijg, Campisi and Lithgow. Molecular and Cellular Biology of Aging. The Gerontological Society of America. 2015. ISBN 978-0-929596-04-4

[2] "Deaths: Final Data for 2019." Center for Disease Control (CDC). National Vital
Statistics Reports, Volume 70, Number 8. July, 2021. Retrieved online at https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-08-508.pdf.

[3] Lopez-Otin, et al. The Hallmarks of Aging. Cell, Volume 153, Issue 6, 6 June 2013, Pages 1194-1217. DOI: https://doi.org/10.1016/j.cell.2013.05.039

[4] Fulop, et al. The integration of inflammaging in age-related diseases. Seminars in Immunology, Volume 40, December 2018, Pages 17-35. DOI: https://doi.org/10.1016/j.smim.2018.09.003

The case against and for extending lifespan

The idea of extending lifespan is a controversial topic. Some believe it is unnatural. Others question if living longer while sick and unhealthy is worth it. Some wonder if the world can sustain more people. These are all important questions. Below I summarize the cases I've heard against and for this research. Then, I'll share my perspective (which you may be able to guess).


The case against research to extend human longevity

  1. Isn’t this unnatural?

  2. Is it worth living longer if you’re just sick and unhealthy? I don’t want to be like grandparents at the end of their life.

  3. Can the world sustain more people? Are we already beyond the world’s carrying capacity?

  4. Will evil dictators remain in power for too long?

  5. Will society become stifled if the old don’t make room for the young?

  6. What if I get bored of my life? Of my significant other?

  7. Will only a select few be able to afford the longevity treatments?

  8. Is it even possible? Human aging is incredibly complex. 


The case for research to extend human longevity

  1. Keep family and friends healthy and alive!

  2. Aging and age-related disease is the leading killer globally.

  3. We are already on board with curing age-related diseases like cancer, dementia and frailty, which are extensions of aging.

  4. We have already more than doubled lifespan in the last 100 years.

  5. We lose so much wisdom, experience and human connection when people die.

  6. Longevity interventions in model organisms and humans show increased healthspan as well as increased lifespan.

  7. The healthcare savings would be enormous, given most money is spent in the last 6 months of life.

  8. If someone doesn’t love life, they don’t have to take the longevity treatments.

  9. Healthcare innovations typically get shared broadly over time. For example, global average life expectancy is around 70 years, including lower-income countries, vs. 75 years in the United States.


My perspective: I want my family and friends to stay healthy and alive for as long as possible. I love life and I want to keep living. I believe in technology development and global progress over the last 150 years has been on average very good for humanity in both rich and lower-income countries. I believe this will continue if we keep making amazing technologies and innovations like lifespan extension.


Species that live longer than humans

I believe humans can have 200+ year lifespans/healthspans. One big reason is that other species already do it.

For example, ocean quahogs live for 200+ years. Greenland sharks live for 250-500 years. Redwood trees can live for over 3,000 years. Bristlecone pines can live for 5,000 years.

Some species of rockfish live for 11 years on average. Some live for 200+ years. Why?

In fact, a study from Sudmant Lab (Science, 2021) studied 88 species of rockfish with various lifespans to identify genetic drivers of lifespan. They found that immunity and DNA repair pathways were associated with longer life. They posited that inflammation may have a major role in aging. 

Evolution has figured out long lifespan already. Let's see what we can learn.

There are a few questions I'd like to explore:

  1. What is the full list of organisms that live for 100s of years?
  2. How they do they do it?
  3. Why did they evolve that way?
  4. What can humans do to mimic this? e.g. gene editing for better DNA repair? 


References:

Kolora, et al. Origins and evolution of extreme life span in Pacific Ocean rockfishes. Science, 11 Nov 2021, Vol 374, Issue 6569, pp. 842-847. DOI: 10.1126/science.abg5332